Evidence for asymmetric intra substantia nigra functional connectivity—application to basal ganglia processing

Doron, Omer; Goelman, Gadi

doi:10.1016/j.neuroimage.2009.11.032

Cited by 12 publications

(8 citation statements)

References 21 publications

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“…Manganese accumulation in distant sites also depends on the length of the pathways and on the number of synapses on the way (Revital et al. ,2008; Doron & Goelman, 2009). These latter two factors are assumed to be constant between groups, enabling the comparison of manganese accumulation among groups.…”

Section: Discussionmentioning

confidence: 99%

The habenula couples the dopaminergic and the serotonergic systems: application to depression in Parkinson’s disease

Sourani

Eitan

Gordon

et al. 2012

Eur J of Neuroscience

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A high percentage of patients with Parkinson's disease suffer from depression in addition to their motor disabilities. However, the etiology of this depression and its relation to Parkinson's disease are unknown. Within the framework of the monoamine deficiency hypothesis of depression, we propose that the dopaminergic and serotonergic systems are coupled by the lateral habenula, and argue that altered basal ganglia activity leads to lateral habenula hyperactivity, which in turn down-regulates the serotonergic system, resulting in depressive symptoms in patients with Parkinson's disease. We tested this hypothesis using the unilateral 6-hydroxydopamine hemiparkinsonian rat model of Parkinson's disease. Behavior was assessed using the novelty suppressed feeding and forced swim tests, and the effective connectivity of the serotonergic system was estimated by manganese-enhanced magnetic resonance imaging of the raphe nuclei. The results show depression-like behaviors and reduced raphe connectivity with the lateral habenula, dentate gyrus of the hippocampus, thalamus and hypothalamus in the 6-hydroxydopamine rat groups. More importantly, partial restoration of the raphe connectivity and partial normalization of behavior were achieved by dopamine replacement therapy (apomorphine, 10 mg/kg, s.c. daily). Furthermore, nearly complete behavioral normalization was reached after a bilateral electric lesion of the lateral habenula. These findings provide a plausible link between Parkinson's disease and depression and open up avenues for new therapeutic interventions in depression and possibly in Parkinson's disease.

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Section: Discussionmentioning

confidence: 99%

The habenula couples the dopaminergic and the serotonergic systems: application to depression in Parkinson’s disease

Sourani

Eitan

Gordon

et al. 2012

Eur J of Neuroscience

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“…Behavioral work (Coombes et al, 2007) has shown that emotion impacts the speed with which ballistic force is initiated as a function of the impact on centrally driven processes (i.e., cognition, perception), as compared with peripheral processes (i.e., musculature and motor unit recruitment). Furthermore, animal retrograde and anterograde tracing studies (Haber, 2003) and human imaging work (Doron & Goelman, 2010; Schmidt et al, 2009) suggest that circuits involving the basal ganglia and frontal cortex are critical to the integration of limbic and motor circuits. Nonreciprocal cortico-cortical and corticothalamic pathways may link multiple frontal cortical areas and functional basal ganglia cortical loops, respectively (Haber & Calzavara, 2009; McFarland & Haber, 2002; Schmidt et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Emotional state affects gait initiation in individuals with Parkinson’s disease

Naugle

Hass

Bowers

et al. 2011

Cogn Affect Behav Neurosci

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The purpose of the present study was to determine the impact of manipulating emotional state on gait initiation in persons with Parkinson’s disease (PD) and healthy older adults. Following the presentation of pictures that are known to elicit specific emotional responses, participants initiated gait and continued to walk for several steps at their normal pace. Reaction time, the displacement and velocity of the center of pressure (COP) trajectory during the preparatory postural adjustments, and length and velocity of the first two steps were measured. Analysis of the gait initiation measures revealed that exposure to (1) threatening pictures, relative to all other pictures, speeded the initiation of gait for PD patients and healthy older adults; (2) approach-oriented emotional pictures (erotic and happy people), relative to withdrawal-oriented pictures, facilitated the anticipatory postural adjustments of gait initiation for PD patients and healthy older adults, as evidenced by greater displacement and velocity of the COP movement; and (3) emotional pictures modulated gait initiation parameters in PD patients to the same degree as in healthy older adults. Collectively, these findings hold significant implications for understanding the circuitry underlying the manner by which emotions modulate movement and for the development of emotion-based interventions designed to maximize improvements in gait initiation for individuals with PD.

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“…In its simplest characterization, these projections are segregated into limbic, associative and sensorimotor loops; the latter represented by afferents from the sensory and motor cortical regions to the dorsal lateral striatum (posterior putamen in primates, DLS/PP hereafter). Evidence is accumulating that these loops are interconnected, facilitating progressive processing and learning across striatal compartments (Doron and Goelman, 2010; Draganski et al, 2008; Haber, 2003; Joel and Weiner, 1994; McGeorge and Faull, 1989; Parent, 1990). Though the larger selective gain framework proposed is relevant to the entire basal ganglia system, the current discussion will be limited to the sensorimotor circuit as the DLS/PP is a primary site of dopamine denervation in PD (Bernheimer et al, 1973; Graybiel et al, 1990; Hornykiewicz, 2001; Kish et al, 1988).…”

Section: Models Of the Basal Ganglia And The Pathophysiology Of Pdmentioning

confidence: 99%

Preservation of function in Parkinson's disease: What's learning got to do with it?

Beeler

2011

Brain Research

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Dopamine denervation gives rise to abnormal corticostriatal plasticity; however, its role in the symptoms and progression of Parkinson’s disease (PD) has not been articulated or incorporated into current clinical models. The ‘integrative selective gain’ framework proposed here integrates dopaminergic mechanisms known to modulate basal ganglia throughput into a single conceptual framework: (1) synaptic weights, the neural instantiation of accumulated experience and skill modulated by dopamine-dependent plasticity and (2) system gain, the operating parameters of the basal ganglia, modulated by dopamine’s on-line effects on cell excitability, glutamatergic transmission and the balance between facilitatory and inhibitory pathways. Within this framework and based on recent work, a hypothesis is presented that prior synaptic weights and established skills can facilitate motor performance and preserve function despite diminished dopamine; however, dopamine denervation induces aberrant corticostriatal plasticity that degrades established synaptic weights and replaces them with inappropriate, inhibitory learning that inverts the function of the basal ganglia resulting in ‘anti-optimization’ of motor performance. Consequently, mitigating aberrant corticostriatal plasticity represents an important therapeutic objective, as reflected in the long-duration response to levodopa, reinterpreted here as the correction of aberrant learning. It is proposed that viewing aberrant corticostriatal plasticity and learning as a provisional endophenotype of PD would facilitate investigation of this hypothesis.

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Evidence for asymmetric intra substantia nigra functional connectivity—application to basal ganglia processing

Cited by 12 publications

References 21 publications

The habenula couples the dopaminergic and the serotonergic systems: application to depression in Parkinson’s disease

The habenula couples the dopaminergic and the serotonergic systems: application to depression in Parkinson’s disease

Emotional state affects gait initiation in individuals with Parkinson’s disease

Preservation of function in Parkinson's disease: What's learning got to do with it?

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